Cells exist within a complex microenvironment consisting of soluble factors (e.g. growth factors, cytokines, and chemokines), an insoluble extracellular matrix which contains proteins for cell adhesion and cell-matrix interactions, and neighboring cells that allow for extensive cell-cell interactions (Lutolf, M. P., Hubbell, J. A., et al., 2005, Nat. Biotechnol., vol. 23, no. 1, p. 47). In cell culture, the microenvironment experienced by the cells can reflect the physiological relevance to in vivo environment and affect cellular behavior (Bhadriraju, K., Chen, C. S., 2002, Drug Discovery Today, vol. 7, no. 11, p. 612). Currently, plenty of powerful tools have been developed at our convenience to create controllable microenvironments that mimic in vivo situations for experimental and therapeutic applications. Progenitor and stem cells for regeneration of desired tissue act in synergy with the soluble factors present in the extracellular microenvironment to navigate multiple differentiation pathways and produce corresponding cell types (Langer, R., Vacanti, J. P., 1993, Science, vol. 260, no. 5110, p. 920). Thus, the microenvironment experienced by stem cells, or known as stem cell niche, is considered to be meaningful in tissue engineering.
Bhadriraju, K. and Chen, C. S. (2002, Drug Discovery Today, vol. 7, no. 11, p. 612) has demonstrated that engineering in vivo-like cultures by creating cellular microenvironments can improve cell-based drug testing.
In order to create more in vivo-like microenvironments for cell culture, both natural and synthetic biomaterials have been chosen for fabricating platforms. Natural ECM, such as Matrigel™ (Kleinman, H. K., Martin, G. R., 2005, Semin. Cancer Biol., vol. 15, no. 5, p. 378) and small intestinal submucosa (SIS) (Badylak, S. F., 2004, Transplat Immunol., vol. 12, no. 3, p. 367), which contain a variety of encapsulated growth factors, have been isolated. They can serve as valuable tools to study the interplay between microenvironments and consequent cellular responses. It has been discovered that vascular endothelial cells cultured in Matrigel™ are able to form capillaries with a central lumen (Grant, D. S., Tashiro, K., 1989, Cell, vol. 58, no. 5, p. 933). However, natural systems complicate the process of identifying the role of individual factors in tissue formation.
Therefore, a need exists to provide further systems which allow creation of in vivo like cell micro environments.